This invention relates to human nerve growth factor.
Nerve growth factor ("NGF") is a polypeptide that is important for the differentiation and survival of sympathetic, sensory, and central cholinergic neurons. Studies in non-human animals have suggested that NGF may be beneficial for the treatment of human diseases, including Alzheimer's and other degenerative diseases, stroke, peripheral nerve injuries and neuropathies, and for post surgical support. Human NGF ("hNGF") is a rare polypeptide in human tissues, and derivation of hNGF from human tissues cannot provide amounts sufficient to supply the potential therapeutic and research needs.
Mature NGFs are known to be derived from prepro-NGFs by proteolytic cleavage. At the 3' end of the NGF gene from rat, chicken, bovine, and human is a large exon ("exon 4") which encodes 243 amino acids of the prepro NGF. Three additional short 5' exons are known in the mouse NGF gene. F. Hallbook et al., Mol. Cell. Biol., Vol. 8, pp. 452-56 (1988), describes using a mammalian expression vector system for synthesis, from fragments of the rat NGF gene or from the chicken NGF gene, of a recombinant NGF that is similar to NGF purified from mouse submandibular gland. The chicken NGF construct of Hallbook et al. includes the 3' exon of the chicken NGF gene, and their rat NGF construct includes a 771-bp fragment from the 3' exon of the rat NGF gene.
European Patent Publication No. 0 121 338 describes expressing human .beta.-NGF in E. coli as a mature polypeptide, using a mature NGF-encoding fragment of the human NGF gene.